Two-photon microscopy is a non-invasive biological imaging technique that can be used to selectively image cellular activity and photosensitizer localization within highly scattering epithelial tissues at depths of ~200 microns with submicron resolution. The principal objective of this study is to develop a model system for understanding the impact of photodynamic therapy on matrix remodeling in biological tissues. An artificial tissue model (RAFT) composed of collagen, embedded fibroblasts, and macrophage cells has been developed for this purpose. TPM is utilized to monitor extracellular matrix remodeling following PDT by imaging collagen/elastin autofluorescence. Selective uptake of photosensitizers by specific cellular components of the matrix can also be visualized by TPM. Results of molecular assays suggest that variations in TPM derived matrix signals correlate with PDT induced cytokine production.